Are Sugar Pills Better than Antidepressant Drugs?

Do Antidepressant Drugs Really Work.jpg

We've learned that exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression (in my video Exercise vs. Drugs for Depression). But how much is that really saying? How effective are antidepressant drugs in the first place?

A recent meta-analysis sparked huge scientific and public controversy by stating that the placebo effect can explain the apparent clinical benefits of antidepressants. But aren't there thousands of clinical trials providing compelling evidence for antidepressant effectiveness? If a meta-analysis compiles together all the best published research, how could it say they don't work much better than sugar pills?

The key word is "published."

What if a drug company decided only to publish studies that showed a positive effect, but quietly shelved and concealed any studies showing the drug didn't work? If you didn't know any better, you'd look at the published medical literature and think "Wow, this drug is great." And what if all the drug companies did that? To find out if this was the case, researchers applied to the FDA under the Freedom of Information Act to get access to the published and unpublished studies submitted by pharmaceutical companies, and what they found was shocking.

According to the published literature, the results of nearly all the trials of antidepressants were positive, meaning they worked. In contrast, FDA analysis of the trial data showed only roughly half of the trials had positive results. In other words, about half the studies showed the drugs didn't work. Thus, when published and unpublished data are combined, they fail to show a clinically significant advantage for antidepressant medication over a sugar pill. Not publishing negative results undermines evidence-based medicine and puts millions of patients at risk for using ineffective or unsafe drugs, and this was the case with these antidepressant drugs.

These revelations hit first in 2008. Prozac, Serzone, Paxil and Effexor worked, but so did sugar pills, and the difference between the drug and placebo was small. That was 2008. Where were we by 2014? Analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits of antidepressants are due to the placebo effect. And what's even worse, Freedom of Information Act documents show the FDA knew about it but made an explicit decision to keep this information from the public and from prescribing physicians.

How could drug companies get away with this?

The pharmaceutical industry is considered the most profitable and politically influential industry in the United States, and mental illness can be thought of as the drug industry's golden goose: incurable, common, long term and involving multiple medications. Antidepressant medications are prescribed to 8.7 percent of the U.S. population. It's a multi-billion dollar market.

To summarize, there is a strong therapeutic response to antidepressant medication; it's just that the response to placebo is almost as strong. Indeed, antidepressants offer substantial benefits to millions of people suffering from depression, and to cast them as ineffective is inaccurate. Just because they may not work better than fake pills doesn't mean they don't work. It's like homeopathy--just because it doesn't work better than the sugar pills, doesn't mean that homeopathy doesn't work. The placebo effect is real and powerful.

In one psychopharmacology journal, a psychiatrist funded by the Prozac company defends the drugs stating, "A key issue is disregarded by the naysaying critics. If the patient is benefiting from antidepressant treatment does it matter whether this is being achieved via drug or placebo effects?"

Of course it matters!

Among the side effects of antidepressants are: sexual dysfunction in up to three quarters of people, long-term weight gain, insomnia, nausea and diarrhea. About one in five show withdrawal symptoms when they try to quit. And perhaps more tragically, the drugs may make people more likely to become depressed in the future. Let me say that again: People are more likely to become depressed after treatment by antidepressants than after treatment by other means - including placebo.

So if doctors are willing to give patients placebo-equivalent treatments, maybe it'd be better for them to just lie to patients and give them actual sugar pills. Yes, that involves deception, but isn't that preferable than deception with a side of side effects? See more on this in my video Do Antidepressant Drugs Really Work?

If different treatments are equally effective, then choice should be based on risk and harm, and of all of the available treatments, antidepressant drugs may be among the riskiest and most harmful. If they are to be used at all, it should be as a last resort, when depression is extremely severe and all other treatment alternatives have been tried and failed.

Antidepressants may not work better than placebo for mild and moderate depression, but for very severe depression, the drugs do beat out sugar pills. But that's just a small fraction of the people taking these drugs. That means that the vast majority of depressed patients--as many as nine out of ten--are being prescribed medications that have negligible benefits to them.

Too many doctors quickly decide upon a depression diagnosis without necessarily listening to what the patient has to say and end up putting them on antidepressants without considering alternatives. And fortunately, there are effective alternatives. Physical exercise, for example can have lasting effects, and if that turns out to also be a placebo effect, it is at least a placebo with an enviable list of side effects. Whereas side effects of antidepressants include things like sexual dysfunction and insomnia, side effects of exercise include enhanced libido, better sleep, decreased body fat, improved muscle tone and a longer life.


There are other ways meta-analyses can be misleading. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

More on the ethical challenges facing doctors and whether or not to prescribe sugar pills in The Lie That Heals: Should Doctors Give Placebos?

I've used the Freedom of Information Act myself to get access to behind the scenes industry shenanigans. See, for example, what I found out about the egg industry in Who Says Eggs Aren't Healthy or Safe? and Eggs and Cholesterol: Patently False and Misleading Claims.

This isn't the only case of the medical profession overselling the benefits of drugs. See How Smoking in 1956 is Like Eating in 2016, The Actual Benefit of Diet vs. Drugs and Why Prevention is Worth a Ton of Cure (though if you're worried about your mood they might make you even more depressed!)

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: GraphicStock. This image has been modified.

Original Link

Are Sugar Pills Better than Antidepressant Drugs?

Do Antidepressant Drugs Really Work.jpg

We've learned that exercise compares favorably to antidepressant medications as a first-line treatment for mild to moderate depression (in my video Exercise vs. Drugs for Depression). But how much is that really saying? How effective are antidepressant drugs in the first place?

A recent meta-analysis sparked huge scientific and public controversy by stating that the placebo effect can explain the apparent clinical benefits of antidepressants. But aren't there thousands of clinical trials providing compelling evidence for antidepressant effectiveness? If a meta-analysis compiles together all the best published research, how could it say they don't work much better than sugar pills?

The key word is "published."

What if a drug company decided only to publish studies that showed a positive effect, but quietly shelved and concealed any studies showing the drug didn't work? If you didn't know any better, you'd look at the published medical literature and think "Wow, this drug is great." And what if all the drug companies did that? To find out if this was the case, researchers applied to the FDA under the Freedom of Information Act to get access to the published and unpublished studies submitted by pharmaceutical companies, and what they found was shocking.

According to the published literature, the results of nearly all the trials of antidepressants were positive, meaning they worked. In contrast, FDA analysis of the trial data showed only roughly half of the trials had positive results. In other words, about half the studies showed the drugs didn't work. Thus, when published and unpublished data are combined, they fail to show a clinically significant advantage for antidepressant medication over a sugar pill. Not publishing negative results undermines evidence-based medicine and puts millions of patients at risk for using ineffective or unsafe drugs, and this was the case with these antidepressant drugs.

These revelations hit first in 2008. Prozac, Serzone, Paxil and Effexor worked, but so did sugar pills, and the difference between the drug and placebo was small. That was 2008. Where were we by 2014? Analyses of the published data and the unpublished data that were hidden by drug companies reveals that most (if not all) of the benefits of antidepressants are due to the placebo effect. And what's even worse, Freedom of Information Act documents show the FDA knew about it but made an explicit decision to keep this information from the public and from prescribing physicians.

How could drug companies get away with this?

The pharmaceutical industry is considered the most profitable and politically influential industry in the United States, and mental illness can be thought of as the drug industry's golden goose: incurable, common, long term and involving multiple medications. Antidepressant medications are prescribed to 8.7 percent of the U.S. population. It's a multi-billion dollar market.

To summarize, there is a strong therapeutic response to antidepressant medication; it's just that the response to placebo is almost as strong. Indeed, antidepressants offer substantial benefits to millions of people suffering from depression, and to cast them as ineffective is inaccurate. Just because they may not work better than fake pills doesn't mean they don't work. It's like homeopathy--just because it doesn't work better than the sugar pills, doesn't mean that homeopathy doesn't work. The placebo effect is real and powerful.

In one psychopharmacology journal, a psychiatrist funded by the Prozac company defends the drugs stating, "A key issue is disregarded by the naysaying critics. If the patient is benefiting from antidepressant treatment does it matter whether this is being achieved via drug or placebo effects?"

Of course it matters!

Among the side effects of antidepressants are: sexual dysfunction in up to three quarters of people, long-term weight gain, insomnia, nausea and diarrhea. About one in five show withdrawal symptoms when they try to quit. And perhaps more tragically, the drugs may make people more likely to become depressed in the future. Let me say that again: People are more likely to become depressed after treatment by antidepressants than after treatment by other means - including placebo.

So if doctors are willing to give patients placebo-equivalent treatments, maybe it'd be better for them to just lie to patients and give them actual sugar pills. Yes, that involves deception, but isn't that preferable than deception with a side of side effects? See more on this in my video Do Antidepressant Drugs Really Work?

If different treatments are equally effective, then choice should be based on risk and harm, and of all of the available treatments, antidepressant drugs may be among the riskiest and most harmful. If they are to be used at all, it should be as a last resort, when depression is extremely severe and all other treatment alternatives have been tried and failed.

Antidepressants may not work better than placebo for mild and moderate depression, but for very severe depression, the drugs do beat out sugar pills. But that's just a small fraction of the people taking these drugs. That means that the vast majority of depressed patients--as many as nine out of ten--are being prescribed medications that have negligible benefits to them.

Too many doctors quickly decide upon a depression diagnosis without necessarily listening to what the patient has to say and end up putting them on antidepressants without considering alternatives. And fortunately, there are effective alternatives. Physical exercise, for example can have lasting effects, and if that turns out to also be a placebo effect, it is at least a placebo with an enviable list of side effects. Whereas side effects of antidepressants include things like sexual dysfunction and insomnia, side effects of exercise include enhanced libido, better sleep, decreased body fat, improved muscle tone and a longer life.


There are other ways meta-analyses can be misleading. See The Saturated Fat Studies: Buttering Up the Public and The Saturated Fat Studies: Set Up to Fail.

More on the ethical challenges facing doctors and whether or not to prescribe sugar pills in The Lie That Heals: Should Doctors Give Placebos?

I've used the Freedom of Information Act myself to get access to behind the scenes industry shenanigans. See, for example, what I found out about the egg industry in Who Says Eggs Aren't Healthy or Safe? and Eggs and Cholesterol: Patently False and Misleading Claims.

This isn't the only case of the medical profession overselling the benefits of drugs. See How Smoking in 1956 is Like Eating in 2016, The Actual Benefit of Diet vs. Drugs and Why Prevention is Worth a Ton of Cure (though if you're worried about your mood they might make you even more depressed!)

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: GraphicStock. This image has been modified.

Original Link

Exercise as a Treatment for Depression

 Exercise vs. Drugs for Depression.jpg

We've known for decades that even a single bout of exercise can elevate our mood, but could it be enough to be used as a treatment for major depression?

We've known that physical activity has been associated with decreased symptoms of depression. For example, if you look at a cross-section of 8,000 people across the country, those that exercised regularly were less likely to have a major depression diagnosis. That's just a snapshot in time, though. In that study, the researcher openly acknowledges this may be a case of reverse causation. Maybe exercise didn't cut down on depression, maybe depression cut down on exercise. The reason depression may be associated with low physical activity is that people may feel too lousy to get out of bed. What we've needed was an interventional study where you take people who are already depressed and randomize them into an exercise intervention.

That is what researchers from Duke University Medical Center did. They randomized men and women over age 50 with major depression to two groups: one who did an aerobic exercise program for four months and another that took an antidepressant drug called Zoloft. In my video Exercise vs. Drugs for Depression you can see a graph of their changes. Before exercise, their Hamilton Depression scores were up around 18 (anything over seven is considered depressed). Within four months, the drug group came down to normal, which are exactly what the drugs are supposed to do. What about the exercise-only group, though? Exercise had the same powerful effect.

The researchers concluded that an exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons, given that they've shown that a group program of aerobic exercise is a feasible and effective treatment for depression, at least for older people.

Not so fast, though.

A "group program?" They had the exercise group folks come in three times a week for a group class. Maybe the only reason the exercise group got better is because they were forced to get out of bed and interact with people--maybe it was the social stimulation and had nothing to do with the actual exercise? Before you could definitively say that exercise can work as well as drugs, what we would need to see is the same study, but with an additional group who exercised alone with no extra social interaction. And those same Duke researchers did just that,

They created the largest exercise trial of patients with major depression conducted to date, and not just including older folks, but other adults as well with three different treatment groups this time: a home exercise group in addition to the supervised group exercise and the drug group as before.

And they all worked about just as well in terms of forcing the depression into remission. So we can say with confidence that exercise is comparable to antidepressant medication in the treatment of patients with major depressive disorder.

Putting all the best studies together, researchers indicate that exercise at least has a moderate antidepressant effect, and at best, exercise has a large effect on reductions in depression symptoms and could be categorized as a very useful and powerful intervention. Unfortunately, while studies support the use of exercise as a treatment for depression, exercise is rarely prescribed as a treatment for this common and debilitating problem.

Exercise may compare favorably to antidepressant medications as a first-line treatment for mild to moderate depression, but how much is that really saying? How effective are antidepressant drugs in the first place? Check out my video Do Antidepressant Drugs Really Work?

For dietary interventions that may improve mood, see:

Exercise can also help with ADHD (Treating ADHD Without Stimulants) and improve immunity (Preserving Immune Function in Athletes With Nutritional Yeast), not to mention extend our lives (Longer Life Within Walking Distance). But what we eat matters: Paleo Diets May Negate Benefits of Exercise.

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: Sally Plank / Flickr. This image has been modified.

Original Link

Exercise as a Treatment for Depression

 Exercise vs. Drugs for Depression.jpg

We've known for decades that even a single bout of exercise can elevate our mood, but could it be enough to be used as a treatment for major depression?

We've known that physical activity has been associated with decreased symptoms of depression. For example, if you look at a cross-section of 8,000 people across the country, those that exercised regularly were less likely to have a major depression diagnosis. That's just a snapshot in time, though. In that study, the researcher openly acknowledges this may be a case of reverse causation. Maybe exercise didn't cut down on depression, maybe depression cut down on exercise. The reason depression may be associated with low physical activity is that people may feel too lousy to get out of bed. What we've needed was an interventional study where you take people who are already depressed and randomize them into an exercise intervention.

That is what researchers from Duke University Medical Center did. They randomized men and women over age 50 with major depression to two groups: one who did an aerobic exercise program for four months and another that took an antidepressant drug called Zoloft. In my video Exercise vs. Drugs for Depression you can see a graph of their changes. Before exercise, their Hamilton Depression scores were up around 18 (anything over seven is considered depressed). Within four months, the drug group came down to normal, which are exactly what the drugs are supposed to do. What about the exercise-only group, though? Exercise had the same powerful effect.

The researchers concluded that an exercise training program may be considered an alternative to antidepressants for treatment of depression in older persons, given that they've shown that a group program of aerobic exercise is a feasible and effective treatment for depression, at least for older people.

Not so fast, though.

A "group program?" They had the exercise group folks come in three times a week for a group class. Maybe the only reason the exercise group got better is because they were forced to get out of bed and interact with people--maybe it was the social stimulation and had nothing to do with the actual exercise? Before you could definitively say that exercise can work as well as drugs, what we would need to see is the same study, but with an additional group who exercised alone with no extra social interaction. And those same Duke researchers did just that,

They created the largest exercise trial of patients with major depression conducted to date, and not just including older folks, but other adults as well with three different treatment groups this time: a home exercise group in addition to the supervised group exercise and the drug group as before.

And they all worked about just as well in terms of forcing the depression into remission. So we can say with confidence that exercise is comparable to antidepressant medication in the treatment of patients with major depressive disorder.

Putting all the best studies together, researchers indicate that exercise at least has a moderate antidepressant effect, and at best, exercise has a large effect on reductions in depression symptoms and could be categorized as a very useful and powerful intervention. Unfortunately, while studies support the use of exercise as a treatment for depression, exercise is rarely prescribed as a treatment for this common and debilitating problem.

Exercise may compare favorably to antidepressant medications as a first-line treatment for mild to moderate depression, but how much is that really saying? How effective are antidepressant drugs in the first place? Check out my video Do Antidepressant Drugs Really Work?

For dietary interventions that may improve mood, see:

Exercise can also help with ADHD (Treating ADHD Without Stimulants) and improve immunity (Preserving Immune Function in Athletes With Nutritional Yeast), not to mention extend our lives (Longer Life Within Walking Distance). But what we eat matters: Paleo Diets May Negate Benefits of Exercise.

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: Sally Plank / Flickr. This image has been modified.

Original Link

What’s the Mediterranean Diet’s Secret?

Why Was Heart Disease Rare in the Mediterranean?.jpg

The Mediterranean Diet is an "in" topic nowadays in both the medical literature and the lay media. As one researcher put it, "Uncritical laudatory coverage is common, but specifics are hard to come by: What is it? Where did it come from? Why is it good? Merits are rarely detailed; possible downsides are never mentioned." So, let's dig in....

After World War II, the government of Greece asked the Rockefeller foundation to come in and assess the situation. Impressed by the low rates of heart disease in the region, nutrition scientist Ancel Keys--after which "K" rations were named--initiated his famous seven countries study. In this study, he found the rate of fatal heart disease on the Greek isle of Crete was 20 times lower than in the United States. They also had the lowest cancer rates and fewest deaths overall. What were they eating? Their diets were more than 90% plant-based, which may explain why coronary heart disease was such a rarity. A rarity, that is, except for a small class of rich people whose diet differed from that of the general population--they ate meat every day instead of every week or two.

So, the heart of the Mediterranean diet is mainly plant-based, and low in meat and dairy, which Keys considered the "major villains in the diet" because of their saturated fat content. Unfortunately, no one is really eating the traditional Mediterranean diet anymore, even in the Mediterranean. The prevalence of coronary heart disease skyrocketed by an order of magnitude within a few decades in Crete, blamed on the increased consumption of meat and cheese at the expense of plant foods.

Everyone is talking about the Mediterranean diet, but few do it properly. People think of pizza or spaghetti with meat sauce, but while "Italian restaurants brag about the healthy measuring in diet, they serve a travesty of it." If no one's really eating this way anymore, how do you study it?

Researchers came up with a variety of Mediterranean diet adherence scoring systems to see if people who are eating more Mediterranean-ish do better. You get maximum points the more plant foods you eat, and effectively you get points deducted by eating just a single serving of meat or dairy a day. So it's no surprise those that eat relatively higher on the scale have a lower risk of heart disease, cancer, and death overall. After all, the Mediterranean diet can be considered to be a "near vegetarian" diet. "As such, it should be expected to produce the well-established health benefits of vegetarian diets." That is, less heart disease, cancer, death, and inflammation; improved arterial function; a lower risk of developing type 2 diabetes; a reduced risk for stroke, depression, and cognitive impairment.

How might it work? I've talked about the elegant studies showing that those who eat plant-based diets have more plant-based compounds, like aspirin, circulating within their systems. Polyphenol phytonutrients in plant foods are associated with a significantly lower risk of dying. Magnesium consumption is also associated with a significantly lower risk of dying, and is found in dark green leafy vegetables, as well as fruits, beans, nuts, soy, and whole grains.

Heme iron, on the other hand--the iron found in blood and muscle--acts as a pro-oxidant and appears to increase the risk of diabetes, whereas plant-based, non-heme iron appears safe. Similarly, with heart disease, animal-based iron was found to significantly increase the risk of coronary heart disease, our number one killer, but not plant-based iron. The Mediterranean diet is protective compared to the Standard American Diet--no question--but any diet rich in whole plant foods and low in animal-fat consumption could be expected to confer protection against many of our leading killers.

Here are some more videos on the Mediterranean Diet:

For more information on heme iron, see Risk Associated With Iron Supplements.

More on magnesium is found in How Do Nuts Prevent Sudden Cardiac Death? and Mineral of the Year--Magnesium.

And more on polyphenols can be seen in videos like How to Slow Brain Aging by Two Years and Juicing Removes More Than Just Fiber.

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: Couleur / Pixabay. This image has been modified.

Original Link

What’s the Mediterranean Diet’s Secret?

Why Was Heart Disease Rare in the Mediterranean?.jpg

The Mediterranean Diet is an "in" topic nowadays in both the medical literature and the lay media. As one researcher put it, "Uncritical laudatory coverage is common, but specifics are hard to come by: What is it? Where did it come from? Why is it good? Merits are rarely detailed; possible downsides are never mentioned." So, let's dig in....

After World War II, the government of Greece asked the Rockefeller foundation to come in and assess the situation. Impressed by the low rates of heart disease in the region, nutrition scientist Ancel Keys--after which "K" rations were named--initiated his famous seven countries study. In this study, he found the rate of fatal heart disease on the Greek isle of Crete was 20 times lower than in the United States. They also had the lowest cancer rates and fewest deaths overall. What were they eating? Their diets were more than 90% plant-based, which may explain why coronary heart disease was such a rarity. A rarity, that is, except for a small class of rich people whose diet differed from that of the general population--they ate meat every day instead of every week or two.

So, the heart of the Mediterranean diet is mainly plant-based, and low in meat and dairy, which Keys considered the "major villains in the diet" because of their saturated fat content. Unfortunately, no one is really eating the traditional Mediterranean diet anymore, even in the Mediterranean. The prevalence of coronary heart disease skyrocketed by an order of magnitude within a few decades in Crete, blamed on the increased consumption of meat and cheese at the expense of plant foods.

Everyone is talking about the Mediterranean diet, but few do it properly. People think of pizza or spaghetti with meat sauce, but while "Italian restaurants brag about the healthy measuring in diet, they serve a travesty of it." If no one's really eating this way anymore, how do you study it?

Researchers came up with a variety of Mediterranean diet adherence scoring systems to see if people who are eating more Mediterranean-ish do better. You get maximum points the more plant foods you eat, and effectively you get points deducted by eating just a single serving of meat or dairy a day. So it's no surprise those that eat relatively higher on the scale have a lower risk of heart disease, cancer, and death overall. After all, the Mediterranean diet can be considered to be a "near vegetarian" diet. "As such, it should be expected to produce the well-established health benefits of vegetarian diets." That is, less heart disease, cancer, death, and inflammation; improved arterial function; a lower risk of developing type 2 diabetes; a reduced risk for stroke, depression, and cognitive impairment.

How might it work? I've talked about the elegant studies showing that those who eat plant-based diets have more plant-based compounds, like aspirin, circulating within their systems. Polyphenol phytonutrients in plant foods are associated with a significantly lower risk of dying. Magnesium consumption is also associated with a significantly lower risk of dying, and is found in dark green leafy vegetables, as well as fruits, beans, nuts, soy, and whole grains.

Heme iron, on the other hand--the iron found in blood and muscle--acts as a pro-oxidant and appears to increase the risk of diabetes, whereas plant-based, non-heme iron appears safe. Similarly, with heart disease, animal-based iron was found to significantly increase the risk of coronary heart disease, our number one killer, but not plant-based iron. The Mediterranean diet is protective compared to the Standard American Diet--no question--but any diet rich in whole plant foods and low in animal-fat consumption could be expected to confer protection against many of our leading killers.

Here are some more videos on the Mediterranean Diet:

For more information on heme iron, see Risk Associated With Iron Supplements.

More on magnesium is found in How Do Nuts Prevent Sudden Cardiac Death? and Mineral of the Year--Magnesium.

And more on polyphenols can be seen in videos like How to Slow Brain Aging by Two Years and Juicing Removes More Than Just Fiber.

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: Couleur / Pixabay. This image has been modified.

Original Link

Reducing Glycotoxin Intake to Help Reduce Brain Loss

Reducing Glycotoxin Intake to Prevent Alzheimer's.jpg

Each of us has about six billion miles of DNA. How does our body keep it from getting all tangled up? There are special proteins called histones, which act like spools with DNA as the thread. Enzymes called sirtuins wrap the DNA around the histones and by doing so, silence whatever genes were in that stretch of DNA, hence their name SIRtuins, which stands for silencing information regulator.

Although they were discovered only about a decade ago, the study of sirtuins "has become one of the most promising areas of biomedicine," since they appear to be involved in promoting healthy aging and longevity. Suppression of this key host defense is considered a central feature of Alzheimer's disease, as shown in Reducing Glycotoxin Intake to Prevent Alzheimer's.

Autopsies of Alzheimer's victims reveal that loss of sirtuin activity is closely associated with the accumulation of the plaques and tangles in the brain that are characteristic of Alzheimer's disease. Sirtuin appears to activate pathways that steer the brain away from the formation of plaque and tangle proteins. "Because a decrease in sirtuin activity can clearly have deleterious effects" on nerve health, researchers are trying to come up with drugs to increase sirtuin activity, but why not just prevent its suppression in the first place?

Glycotoxins in our food suppress sirtuin activity, also known as advanced glycation end products, or AGE's. Our modern diet includes excessive AGE's, which can be neurotoxic. High levels in the blood may predict cognitive decline over time. If you measure the urine levels of glycotoxins flowing through the bodies of older adults, those with the highest levels went on to suffer the greatest cognitive decline over the subsequent nine years.

As we age, our brain literally shrinks. In our 60's and 70's, we lose an average of five cubic centimeters of total brain tissue volume every year, but some people lose more than others. Brain atrophy may be reduced in very healthy individuals, and a few people don't lose any brain at all. Normally we lose about 2% of brain volume every year, but that's just the average. Although the average brain loss for folks in their 70's and 80's was 2.1%, some lost more, some lost less, and some men and women lost none at all over a period of four years.

Researchers in Australia provided the first evidence linking AGEs with this kind of cerebral brain loss. So, limiting one's consumption of these compounds may end up having significant public health benefits. Because sirtuin deficiency is both preventable and reversible by dietary AGE reduction, a therapeutic strategy that includes eating less AGE's may offer a new strategy to combat the epidemic of Alzheimer's.

Some glycotoxins are produced internally, particularly in diabetics, but anyone can get them from smoking and eating, particularly foods high in fat and protein cooked at high temperatures. In my video, Avoiding a Sugary Grave, I listed the 15 foods most contaminated with glycotoxins; mostly chicken, but also pork, beef, and fish, which may help explain why those that eat the most meat may have triple the risk of getting dementia compared to long-time vegetarians. Note there are some relatively high fat and protein plant foods such as nuts and soy products, so I no longer recommend toasting nuts and would steer clear from roasted tofu.

I've covered advanced glycation end-products in Glycotoxins, Bacon, Eggs, and Gestational Diabetes During Pregnancy, and Why is Meat a Risk Factor for Diabetes?.

More on slowing brain aging in How to Slow Brain Aging By Two Years.

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: lightwise © 123RF.com. This image has been modified.

Original Link

Reducing Glycotoxin Intake to Help Reduce Brain Loss

Reducing Glycotoxin Intake to Prevent Alzheimer's.jpg

Each of us has about six billion miles of DNA. How does our body keep it from getting all tangled up? There are special proteins called histones, which act like spools with DNA as the thread. Enzymes called sirtuins wrap the DNA around the histones and by doing so, silence whatever genes were in that stretch of DNA, hence their name SIRtuins, which stands for silencing information regulator.

Although they were discovered only about a decade ago, the study of sirtuins "has become one of the most promising areas of biomedicine," since they appear to be involved in promoting healthy aging and longevity. Suppression of this key host defense is considered a central feature of Alzheimer's disease, as shown in Reducing Glycotoxin Intake to Prevent Alzheimer's.

Autopsies of Alzheimer's victims reveal that loss of sirtuin activity is closely associated with the accumulation of the plaques and tangles in the brain that are characteristic of Alzheimer's disease. Sirtuin appears to activate pathways that steer the brain away from the formation of plaque and tangle proteins. "Because a decrease in sirtuin activity can clearly have deleterious effects" on nerve health, researchers are trying to come up with drugs to increase sirtuin activity, but why not just prevent its suppression in the first place?

Glycotoxins in our food suppress sirtuin activity, also known as advanced glycation end products, or AGE's. Our modern diet includes excessive AGE's, which can be neurotoxic. High levels in the blood may predict cognitive decline over time. If you measure the urine levels of glycotoxins flowing through the bodies of older adults, those with the highest levels went on to suffer the greatest cognitive decline over the subsequent nine years.

As we age, our brain literally shrinks. In our 60's and 70's, we lose an average of five cubic centimeters of total brain tissue volume every year, but some people lose more than others. Brain atrophy may be reduced in very healthy individuals, and a few people don't lose any brain at all. Normally we lose about 2% of brain volume every year, but that's just the average. Although the average brain loss for folks in their 70's and 80's was 2.1%, some lost more, some lost less, and some men and women lost none at all over a period of four years.

Researchers in Australia provided the first evidence linking AGEs with this kind of cerebral brain loss. So, limiting one's consumption of these compounds may end up having significant public health benefits. Because sirtuin deficiency is both preventable and reversible by dietary AGE reduction, a therapeutic strategy that includes eating less AGE's may offer a new strategy to combat the epidemic of Alzheimer's.

Some glycotoxins are produced internally, particularly in diabetics, but anyone can get them from smoking and eating, particularly foods high in fat and protein cooked at high temperatures. In my video, Avoiding a Sugary Grave, I listed the 15 foods most contaminated with glycotoxins; mostly chicken, but also pork, beef, and fish, which may help explain why those that eat the most meat may have triple the risk of getting dementia compared to long-time vegetarians. Note there are some relatively high fat and protein plant foods such as nuts and soy products, so I no longer recommend toasting nuts and would steer clear from roasted tofu.

I've covered advanced glycation end-products in Glycotoxins, Bacon, Eggs, and Gestational Diabetes During Pregnancy, and Why is Meat a Risk Factor for Diabetes?.

More on slowing brain aging in How to Slow Brain Aging By Two Years.

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: lightwise © 123RF.com. This image has been modified.

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Why Some Like Cilantro and Others Hate It

The Cilantro Gene.jpg

One sign of changing U.S. demographics is that salsa has replaced ketchup as America's #1 table condiment. One of the popular salsa ingredients is cilantro, described as one of the "most polarizing and divisive food ingredients known." Some people love it; some people hate it. What's interesting is that the lovers and the haters appear to experience the taste differently. Individuals who like cilantro may describe it as "fresh, fragrant or citrusy, whereas those who dislike cilantro report that it tastes like soap, mold, dirt, or bugs." I don't know how people know what bugs taste like, but rarely are polarizing opinions about flavors so extreme. Maybe it's genetic.

Different ethnic groups do seem to have different rates of cilantro dislike, with Ashkenazi Jews scoring highest on the cilantro hate-o-meter (see The Cilantro Gene). Another clue came from twin studies, that show that identical twins tend to share cilantro preferences, whereas regular fraternal twins do not have such a strong correlation. Our genetic code is so big, though, containing about three billion letters, that to find some cilantro gene you'd have to analyze the DNA of like 10,000 people, and obviously genetic researchers have better things to do...or maybe not.

Researchers performed a genome-wide association study among 14,000 participants who reported whether cilantro tasted soapy, with replication in a distinct set of 11,000 people who declared whether they liked cilantro or not. And lo and behold they found a spot on chromosome 11 that seemed to be a match. What's there? A gene called OR6A2 that enables us to smell certain chemicals like E-(2)-Decenal, a primary constituent of cilantro and also...the defensive secretions of stink bugs. So maybe cilantro does taste like bugs! But, cilantro lovers may be genetic mutants that have an inability to smell the unpleasant compound.

That may actually be an advantage, though, since cilantro is healthy stuff. In fact, that's the justification to do these kinds of studies: to see why some people don't like the taste of healthy foods.

Are the cilantro haters really missing out on much, though? Mother nature has been described as the "oldest and most comprehensive pharmacy of all time," and cilantro--called coriander around most of the world--is one of nature's oldest herbal prescriptions, credited with anti-microbial, anti-oxidant, anti-diabetic, anti-anxiety, and anti-epilepsy properties. However, these are all from preclinical studies, meaning studies done on cells in a test tube or lab animals. Studies like the "Anti-Despair Activity of Cilantro..." in which researchers placed animals in a "despair apparatus" (you don't want to know).

Finally, though, there was a human study, on the anti-arthritis potential of cilantro. There was an earlier study performed in Germany of a lotion made out of cilantro seeds showing it could decrease the redness of a sunburn, demonstrating it had some anti-inflammatory effects )though not as much as an over-the-counter steroid, hydrocortisone, or prescription strength steroid cream). If the cilantro plant is anti-inflammatory, why nto give it to people with osteoarthritis and see if it helps? Researchers gave about 20 sprigs of cilantro daily for two months, and reported a significant drop in ESR--a nonspecific indicator of inflammation--in the cilantro group. How did the patients do clinically, though? The study didn't say, but it did report a rather remarkable 50% drop in uric acid levels, suggesting that huge amounts of cilantro may be useful for those suffering from gout.


The cilantro lovers/haters factoid reminds me of the video Pretty in Pee-nk about the phenomenon of "beeturia," pink urine after beet consumption seen in some people.

For those that don't mind the taste of bugs, I have some nutritional info in Good Grub: The Healthiest Meat and Bug Appétit: Barriers to Entomophagy.

As an Ashkenazim myself, I'm excited to have narrowly escaped a cilantro-less existence!

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: Sally Plank / Flickr. This image has been modified.

Original Link

Why Some Like Cilantro and Others Hate It

The Cilantro Gene.jpg

One sign of changing U.S. demographics is that salsa has replaced ketchup as America's #1 table condiment. One of the popular salsa ingredients is cilantro, described as one of the "most polarizing and divisive food ingredients known." Some people love it; some people hate it. What's interesting is that the lovers and the haters appear to experience the taste differently. Individuals who like cilantro may describe it as "fresh, fragrant or citrusy, whereas those who dislike cilantro report that it tastes like soap, mold, dirt, or bugs." I don't know how people know what bugs taste like, but rarely are polarizing opinions about flavors so extreme. Maybe it's genetic.

Different ethnic groups do seem to have different rates of cilantro dislike, with Ashkenazi Jews scoring highest on the cilantro hate-o-meter (see The Cilantro Gene). Another clue came from twin studies, that show that identical twins tend to share cilantro preferences, whereas regular fraternal twins do not have such a strong correlation. Our genetic code is so big, though, containing about three billion letters, that to find some cilantro gene you'd have to analyze the DNA of like 10,000 people, and obviously genetic researchers have better things to do...or maybe not.

Researchers performed a genome-wide association study among 14,000 participants who reported whether cilantro tasted soapy, with replication in a distinct set of 11,000 people who declared whether they liked cilantro or not. And lo and behold they found a spot on chromosome 11 that seemed to be a match. What's there? A gene called OR6A2 that enables us to smell certain chemicals like E-(2)-Decenal, a primary constituent of cilantro and also...the defensive secretions of stink bugs. So maybe cilantro does taste like bugs! But, cilantro lovers may be genetic mutants that have an inability to smell the unpleasant compound.

That may actually be an advantage, though, since cilantro is healthy stuff. In fact, that's the justification to do these kinds of studies: to see why some people don't like the taste of healthy foods.

Are the cilantro haters really missing out on much, though? Mother nature has been described as the "oldest and most comprehensive pharmacy of all time," and cilantro--called coriander around most of the world--is one of nature's oldest herbal prescriptions, credited with anti-microbial, anti-oxidant, anti-diabetic, anti-anxiety, and anti-epilepsy properties. However, these are all from preclinical studies, meaning studies done on cells in a test tube or lab animals. Studies like the "Anti-Despair Activity of Cilantro..." in which researchers placed animals in a "despair apparatus" (you don't want to know).

Finally, though, there was a human study, on the anti-arthritis potential of cilantro. There was an earlier study performed in Germany of a lotion made out of cilantro seeds showing it could decrease the redness of a sunburn, demonstrating it had some anti-inflammatory effects )though not as much as an over-the-counter steroid, hydrocortisone, or prescription strength steroid cream). If the cilantro plant is anti-inflammatory, why nto give it to people with osteoarthritis and see if it helps? Researchers gave about 20 sprigs of cilantro daily for two months, and reported a significant drop in ESR--a nonspecific indicator of inflammation--in the cilantro group. How did the patients do clinically, though? The study didn't say, but it did report a rather remarkable 50% drop in uric acid levels, suggesting that huge amounts of cilantro may be useful for those suffering from gout.


The cilantro lovers/haters factoid reminds me of the video Pretty in Pee-nk about the phenomenon of "beeturia," pink urine after beet consumption seen in some people.

For those that don't mind the taste of bugs, I have some nutritional info in Good Grub: The Healthiest Meat and Bug Appétit: Barriers to Entomophagy.

As an Ashkenazim myself, I'm excited to have narrowly escaped a cilantro-less existence!

In health,

Michael Greger, M.D.

PS: If you haven't yet, you can subscribe to my free videos here and watch my live, year-in-review presentations:

Image Credit: Sally Plank / Flickr. This image has been modified.

Original Link